DESCRIPTION The firing patterns of neurons (and the cognitive processes they underlie) are shaped by the complex interactions of synaptic inputs with voltage- gated channels, a process termed synaptic integration. Despite the fact that these interactions take place extensively in dendrites, the small size of these structures has hindered their systematic study. The experiments in this proposal will use recent optical advances to make whole-cell patch recordings simultaneously from the soma and dendrites of CA1 pyramidal neurons. One group of experiments will address how voltage- gated Na+, Ca+, and K+ channels influence the propagation of subthreshold excitatory postsynaptic potentials (EPSPs) to the soma. Paired recordings will enable the attenuation of simulated EPSPs between the dendrites and soma to be measured directly. The role of voltage-gated channels will be assessed by determining the effects of various channel blockers on their size and shape of simulated ESPs. A second group of experiments, also using paired dendritic and somatic recordings will examine the integrative manifestations of Ca2+-dependent spiking. Experiments will determine directly the site of Ca/2+ spike initiation, the spatial extent of their influence, their interactions with other voltage- and/or Ca/2+-activated channels, and their direct and indirect effects on the initiation of Na+- dependent action potentials.